Endotoxin (bacterial lipopolysaccharide, LPS) induces acute anterior uveitis after either local or systemic injection in rats or rabbits. The animal model may be relevant to human disease, especially that related to the histocompatibility marker, HLA B27. Work to date has attempted to determine the cellular and humoral mechanisms whereby endotoxin induces ocular inflammation. In pursuit of this goal, we have 1) characterized the pathological and clinical changes associated with this animal model; 2) examined some of the mediators that contribute to it; 3) identified some of the factors in aqueous humor that may initiate the cellular infiltrate in this iris-ciliary body; and 4) documented the paradoxical ability of endotoxin to inhibit inflammation. The purpose of this proposal is to build on these observations. Specifically we intend to 1) identify the receptor on monocytes for the predominant chemoattractant associated with endotoxin-induced uveitis; 2) characterize the ocular inflammatory effects of interleukin-1 and tumor necrosis factor, two endotoxin-induced monocyte products; 3) clarify the mechanism(s) by which endotoxin paradoxically inhibits inflammation; and 4) utilize some novel pharmacologic agents to modify endotoxin-induced uveitis. These pharmacologic approaches include an inhibitor of platelet activating factor, a recombinant protein that inhibits phospholipase A2, an eicosapentaenoic acid diet, and monoclonal antibodies against the core of the endotoxin molecule. These studies should result in an enhanced understanding of ocular inflammation.